B & T Cell Activation & Development, Cytokines, MHC 1 CD40 TNF B7 IL 2 LTB4 CD4 CD8

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• published: 01 Jan 2015
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http://www.stomponstep1.com/b-t-cell-activation-development-cytokines-mhc-1-cd40-tnf-b7-il-2-ltb4-cd4-cd8/ SKIP AHEAD: 1:04 – Intro to the Adaptive Immune Response & Types of Lymphocytes 3:44 – T & B Cell Function & Activation 7:32 – B & T Cell Development (Hematopoietic Stem Cells, Secondary & Primary Lymphoid Organs) 9:36 – Negative Selection through Central & Peripheral Tolerance 11:18 – Major Histocompatibility Complex (MHC 1 & 2) 13:44 – T Cell Activation: Helper CD4 & Cytotoxic CD8 16:06 – B Cell Activation: T Cell Dependent & Independent 17:54 – Cytokines: Interleukin 1 (IL-1), IL-2, IL-8, Tumor Necrosis Factor (TNF), Interferon There are 2 main types of T-Cell, each of which is part of Cell-Mediated Immunity. CD8 T-cells, named for its CD8 surface marker, are the “Cytotoxic” T-Cell. These lymphocytes release perforin and granzyme to cause lysis of infected cells, similar to how NK cells function. These CD8 cells cause apoptosis of cells that are infected by intracellular pathogens (primarily viruses and intracellular bacteria like chlamydia). Cytotoxic T-Cells also play a role in triggering apoptosis of cancerous cells. CD4 T-Cells, named for their CD4 surface marker, are referred to as the “Helper” T-cells. They do not fight pathogens directly, but help various other cells to do so by releasing cytokines signals. There are 2 subtypes of CD4 Helper T-Cells, Th1 and Th2. Th1 Helper T-Cells primarily activate cytotoxic CD8 T-cells and Macrophages. Th2 helper T-cells primarily activate B-Cells. Both T-Cells & B-Cells begin life in the bone marrow and arise from multipotent hematopoietic stem cells. Immature B-Cells remain in the bone marrow to complete maturation (Think B for Bone Marrow), while the immature T-Cells leave the bone marrow and travel to the thymus to complete maturation (Think T for Thymus). The bone marrow and thymus are referred to as Primary Lymphoid Organs. These Primary Lymphoid Organs are where B-Cells and T-Cells differentiate and mature. Absence of a primary lymphoid organ, such as the absence of the thymus in DiGeorge Syndrome, prevents the normal development of white blood cells and can lead to immunodeficiency. Once mature, B-Cells and T-Cells move to Secondary Lymphoid Organs such as the lymph node and spleen. This is where these cells come into contact with foreign pathogens. If the pathogen the cell can interact with is present the cell will be activated. After activation the cells proliferate making clones of themselves that are all capable of recognizing and fighting against the same antigen. However, not all T & B Cells will be activated. A large majority of these cells will not encounter the type of foreign material they recognize. If the foreign material the B or T Cell can fight against isn’t present in the body there is no need to be activated. The foreign material or pathogen that the T & B Cells recognize is determined by their unique surface receptors. An Antigen is the specific structural sequence the receptor can bind to. For example, a protein fragment of a pathogen you want to mount an immune response against. All of the receptors on a given T or B Cell are the same and recognize the same antigen. When the receptor binds to the appropriate antigen it signals the cell to become activated and proliferate. You need a nearly infinite variability in these receptors so that you can fight almost any pathogen encountered. Therefore, while the leukocytes are in the primary lymphoid organs a wide variety of receptor variability is randomly generated through VDJ Recombination. This change in the portion of the genome that encodes for the cell’s receptors allows the different leukocytes to interact with a huge variety of antigens. The problem with randomly generating surface receptors is that some of these leukocytes will now be able to bind the body’s own cells. If these self-reactive lymphocytes where activated they would cause autoimmune damage where the immune system targets the body’s tissue instead of foreign material. The body has a 2 step process for preventing this called Negative Selection. In the primary lymphoid organs self-reactive leukocytes are removed by Central Tolerance (AKA Clonal Deletion). Developing T & B lymphocytes that interact too strongly with self-antigens undergo apoptosis or programmed cell death. In the secondary lymphoid organs there is a similar process called Peripheral Tolerance or Clonal Anergy. Here self-reactive T or B Cells that bind to soluble self-antigens undergo anergy. Anergy is when a cell is prevented from becoming active. These anergic cells are not killed, but they are prevented from proliferating. The text for this video is too long and exceeds the maximum allowed length by youtube. To see the full text please go here http://www.stomponstep1.com/b-t-cell-activation-development-cytokines-mhc-1-cd40-tnf-b7-il-2-ltb4-cd4-cd8/